The long-term objective of this research is to understand the role of nutritional factors in the development of atherosclerosis and cholesterol gallstones in animal models. The aims of this proposal are to measure the effects of dietary factors, i.e. fat, cholesterol, and protein, and of gender and sex hormones on lipoprotein composition and metabolism and on bile composition and formation. We will study the effects in rhesus monkeys of low protein diets on plasma lipoproteins and try to explain the increased concentrations of very low and high density-2 lipoproteins that we have observed. We will extend our studies of atherosclerosis and cholesterol gallstones in squirrel monkeys to diets with relatively low levels of cholesterol and with very unsaturated fats. Different levels of estrogen will be given to gonadectomized squirrel monkeys to determine their effects on lipoprotein composition and metabolism, and longterm effects of selected dosages on lipoproteins, arterial and biliary lipids, and incidence of gallstones will be determined. We will also study lipoproteins and bile of gallstone-susceptible and -resistant populations of squirrel monkeys. Lipoproteins metabolism will be measured in primary cultures of rabbit hepatocytes. We will study receptors of high and low density lipoproteins and determine the effects of dietary factors on the lipoprotein donors and of estrogen on the hepatocyte donors. We will compare the uptake of the protein and lipid components of lipoproteins. We will attempt to culture nonparenchymal liver cells, particularly Kupffer cells, and compare their lipoprotein metabilism to that of hepatocytes. We will also compare lipoprotein receptor activity in liver homogenates to that in isolated hepatocytes. Plasma lipoprotein concentrations and compositions will be compared to glucose metabolism and levels of plasma hormones in diabetic and nondiabetic Macaca nigra that have been fed diets with different kinds and levels of fat and levels of cholesterol. The object is to determine if the susceptibility of diabetic monkeys to atherosclerosis is related to their plasma lipoprotein or hormone levels, e.g., insulin, glucagon, or growth hormone.